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Biomedical subjects

M A Powers

Publications and source records attributed to M A Powers.

At least 19 recordsLinked to original sources
PubMed2001

Function of the Drosophila TGF-alpha homolog Spitz is controlled by Star and interacts directly with Star.

Drosophila Spitz is a homolog of transforming growth factor alpha (TGF-alpha) and is an activating ligand for the EGF receptor (Egfr). It has been shown that Star is required for Spitz activity. Here we show that Star is quantitatively limiting for Spitz production during eye development. We also show that Star and Spitz proteins colocalize in Spitz sending cells and that this association is not coincident with the site of translation--consistent with a function for Star in Spitz processing or transmission. Finally, we have defined minimal sequences within both Spitz and Star that mediate a direct interaction and show that this binding can occur in vivo.

Amino Acid Sequence↗
PubMed1999

The nucleoporin nup153 plays a critical role in multiple types of nuclear export.

The fundamental process of nucleocytoplasmic transport takes place through the nuclear pore. Peripheral pore structures are presumably poised to interact with transport receptors and their cargo as these receptor complexes first encounter the pore. One such peripheral structure likely to play an important role in nuclear export is the basket structure located on the nuclear side of the pore. At present, Nup153 is the only nucleoporin known to localize to the surface of this basket, suggesting that Nup153 is potentially one of the first pore components an RNA or protein encounters during export. In this study, anti-Nup153 antibodies were used to probe the role of Nup153 in nuclear export in Xenopus oocytes. We found that Nup153 antibodies block three major classes of RNA export, that of snRNA, mRNA, and 5S rRNA. Nup153 antibodies also block the NES protein export pathway, specifically the export of the HIV Rev protein, as well as Rev-dependent RNA export. Not all export was blocked; Nup153 antibodies did not impede the export of tRNA or the recycling of importin beta to the cytoplasm. The specific antibodies used here also did not affect nuclear import, whether mediated by importin alpha/beta or by transportin. Overall, the results indicate that Nup153 is crucial to multiple classes of RNA and protein export, being involved at a vital juncture point in their export pathways. This juncture point appears to be one that is bypassed by tRNA during its export. We asked whether a physical interaction between RNA and Nup153 could be observed, using homoribopolymers as sequence-independent probes for interaction. Nup153, unlike four other nucleoporins including Nup98, associated strongly with poly(G) and significantly with poly(U). Thus, Nup153 is unique among the nucleoporins tested in its ability to interact with RNA and must do so either directly or indirectly through an adaptor protein. These results suggest a unique mechanistic role for Nup153 in the export of multiple cargos.

Animals↗
PubMed1998

Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1.

Activation of the Cyclin B/Cdc2 kinase complex triggers entry into mitosis in all eukaryotic cells. Cyclin B1 localization changes dramatically during the cell cycle, precipitously transiting from the cytoplasm to the nucleus at the beginning of mitosis. Presumably, this relocalization promotes the phosphorylation of nuclear targets critical for chromatin condensation and nuclear envelope breakdown. We show here that the previously characterized cytoplasmic retention sequence of Cyclin B1, responsible for its interphase cytoplasmic localization, is actually an autonomous nuclear export sequence, capable of directing nuclear export of a heterologous protein, and able to bind specifically to the recently identified export mediator, CRM1. We propose that the observed cytoplasmic localization of Cyclin B1 during interphase reflects the equilibrium between ongoing nuclear import and rapid CRM1-mediated export. In support of this hypothesis, we found that treatment of cells with leptomycin B, which disrupted Cyclin B1-CRM1 interactions, led to a marked nuclear accumulation of Cyclin B1. In mitosis, Cyclin B1 undergoes phosphorylation at several sites, a subset of which have been proposed to play a role in Cyclin B1 accumulation in the nucleus. Both CRM1 binding and the ability to direct nuclear export were affected by mutation of these phosphorylation sites; thus, we propose that Cyclin B1 phosphorylation at the G2/M transition prevents its interaction with CRM1, thereby reducing nuclear export and facilitating nuclear accumulation.

Animals↗
PubMed1997

Inhibition of mRNA export in vertebrate cells by nuclear export signal conjugates.

Leucine-rich nuclear export signals (NESs) are recognized by the NES receptor exportin 1 and are central to the export of multiple shuttling proteins and RNAs. The export of messenger RNA in vertebrates was, however, thought to occur by a different pathway, because inhibition by injection of a synthetic Rev NES conjugate could not be demonstrated. Here we find that peptide conjugates composed of the NES of either protein kinase A inhibitor protein (PKI) or the HIV-1 Rev protein, when coupled to human serum albumin, are potent inhibitors of mRNA and small nuclear RNA export. These results provide direct evidence that mRNA export in vertebrates depends on interactions between an NES and its cognate NES receptors. PKI NES conjugates are significantly more efficient at inhibiting RNA export than are REV NES conjugates, indicating that different NESs may have different abilities to promote protein and RNA export. Surprisingly, an expected control conjugate containing the mutant Rev NES sequence M10 strongly inhibited the export of intronless dihydrofolate reductase mRNA. Nuclear injection of NES peptide conjugates led to mislocalization to the nucleus of 10-20% of the cytoplasmic Ran GTPase-binding protein (RanBP1) indicating that RanBP1 shuttles between the nucleus and the cytoplasm via an NES pathway. These results demonstrate that in vertebrates the export of mRNA, like that of small nuclear RNA, 5S rRNA, and transport factors such as RanBP1, employs NES-mediated molecular machinery.

Amino Acid Sequence↗
PubMed1997

The vertebrate GLFG nucleoporin, Nup98, is an essential component of multiple RNA export pathways.

The 97-kD O-linked glycoprotein, Nup98, is a component of the Xenopus laevis nuclear pore complex and the only vertebrate GLFG nucleoporin identified (Powers, M.A., C. Macauley, F. Masiarz, and D.J. Forbes. 1995. J. Cell Biol. 128:721-736). We have investigated possible roles of xNup98 in the nucleocytoplasmic transport of proteins and RNAs by analyzing the consequences of injecting monospecific polyclonal antibodies to xNup98 into X. laevis oocytes. We show here that nuclear injection of anti-xNup98 inhibited the export of multiple classes of RNAs, including snRNAs, 5S RNA, large ribosomal RNAs, and mRNA. In contrast, the export of tRNA was unaffected. Injection of anti-xNup98 into the oocyte cytoplasm had no effect on export of any of the RNAs. Significantly, nuclear injection of anti-xNup98 antibodies did not inhibit import of either karyophilic proteins or snRNPs. This latter result is in agreement with our previous finding that Nup98 is not an essential element of the protein import pathway. Thus, Nup98 plays a role specifically in RNA export from the nucleus, and it appears to be an essential component of multiple RNA export pathways.

Animals↗
PubMed1996

Peripheral blood mononuclear cells from sheep infected with a variant of bovine leukemia virus synthesize envelope glycoproteins but fail to induce syncytia in culture.

Peripheral blood mononuclear cells (PBMCs) infected with the oncogenic retrovirus bovine leukemia virus (BLV) produce virus when cultured briefly. BLV can be transmitted in cocultures to adherent susceptible cells, which become infected, express viral proteins, and fuse into multinucleated syncytia several days later. PBMCs from 3 of 10 BLV-infected sheep displayed a lifelong deficiency in induction of syncytium formation among indicator cells in culture, although large numbers of PBMCs synthesized viral transcripts or capsid protein. Since the infected, syncytium-deficient PBMCs were > or = 97% B cells, the deficiency could not be attributed to altered host cell tropism. The syncytium-deficient phenotype was recapitulated in newly infected sheep, demonstrating that this property is regulated by the viral genotype. The alteration in the BLV genome delayed but did not prohibit the establishment of BLV infection in vivo. Envelope glycoproteins were synthesized in syncytium-deficient PBMCs, translocated to the cell surface, and incorporated into virions. However, monoclonal antibodies specific for the BLV surface glycoprotein did not stain fixed PBMCs of the syncytium-deficient phenotype. Moreover, an animal with syncytium-deficient PBMCs had lower titers of neutralizing antibodies throughout the first 5 years of infection than an animal with similar numbers of infected PBMCs of the syncytium-inducing phenotype. The syncytium-deficient variant productively infected indicator cells at greatly reduced efficiency, showing that the alteration affects an early step in viral entry or replication. These results suggest that the alteration maps in the env gene or in a gene whose product affects the maturation or conformation, and consequently the function, of the envelope protein complex.

Animals↗
PubMed1996

Fat replacers: their use in foods and role in diabetes medical nutrition therapy.

The scientific literature demonstrates that fat replacers have a reasonable certainty of no harm. Whether they help produce desired health outcomes, i.e., decreased risk of coronary heart disease and certain types of cancer related to excess fat intake, weight reduction, changes in lipid profile, improved glycemic control, etc., depends on how individuals use these foods to change food choices and eating behaviors. As Miller and Rolls conclude, ...the use of fat-replaced foods alone should not be expected to produce spontaneous improvements in weight management. Such improvements will still be dependent on long-term behavioral changes that include not only modifications in fat, but also modifications in overall energy intake and increase in energy expenditure. (53) Though it has not been studied, one may conjecture that encouraging people with diabetes to use foods with fat replacers to achieve nutrition management goals requires sufficient education, continuous counseling, and an individual's conscientious commitment and readiness to change food habits.

Diabetes Mellitus↗
PubMed1995

Reconstituted nuclei depleted of a vertebrate GLFG nuclear pore protein, p97, import but are defective in nuclear growth and replication.

Xenopus egg extracts provide a powerful system for in vitro reconstitution of nuclei and analysis of nuclear transport. Such cell-free extracts contain three major N-acetylglucosaminylated proteins: p200, p97, and p60. Both p200 and p60 have been found to be components of the nuclear pore. Here, the role of p97 has been investigated. Xenopus p97 was isolated and antisera were raised and affinity purified. Immunolocalization experiments indicate that p97 is present in a punctate pattern on the nuclear envelope and also in the nuclear interior. Peptide sequence analysis reveals that p97 contains a GLFG motif which defines a family of yeast nuclear pore proteins, as well as a peptide that is identical at 11/15 amino acids to a specific member of the GLFG family, NUP116. An additional peptide is highly homologous to a second sequence found in NUP116 and other members of the yeast GLFG family. A monoclonal antibody to the GLFG domain cross-reacts with a major Xenopus protein of 97 kD and polyclonal antiserum to p97 recognizes the yeast GLFG nucleoporin family. The p97 antiserum was used to immunodeplete Xenopus egg cytosol and p97-deficient nuclei were reconstituted. The p97-depleted nuclei remained largely competent for nuclear protein import. However, in contrast to control nuclei, nuclei deficient in p97 fail to grow in size over time and do not replicate their chromosomal DNA. ssDNA replication in such extracts remains unaffected. Addition of the N-acetylglucosaminylated nuclear proteins of Xenopus or rat reverses these replication and growth defects. The possible role(s) of p97 in these nuclear functions is discussed.

Amino Acid Sequence↗
PubMed1993

Model for dietetics practice and research: the challenge is here, but the journey was not easy.

If, as dietitians, we are to expand our role and influence on patient care and in clinical research (as described by the DCCT model), we need to examine our strengths, obtain expertise in our areas of interest, educate nondietitians and investigators about the benefits of using our skills in the clinical and research environments, and continue to develop our mentoring system. We need to identify our own personal challenges that will make us more effective leaders in health care. Also, we must acknowledge that the journey to reach these new goals will not always be easy, but is tremendously rewarding--personally and professionally.

Blood Glucose↗
PubMed1992

Activation of bovine leukemia virus transcription in lymphocytes from infected sheep: rapid transition through early to late gene expression.

Bovine leukemia virus (BLV) expression is mostly silent in peripheral blood mononuclear cells (PBMCs) of infected animals. However, when infected cells are cultured, they are stimulated to produce virus. We studied viral transcription in PBMCs taken from BLV-infected sheep because the pattern of transcriptional activation in these cells should closely mimic activation of virus expression within mononuclear cells in vivo. BLV transcription was activated as early as 30 min after PBMCs were cultured. Expression was characterized by early and late stages, each distinguished by a unique pattern of cytoplasmic RNAs. In early expression, cytoplasmic viral RNA was exclusively the doubly spliced tax/rex transcript, although all transcripts were present in the nucleus. Early expression gave way rapidly to late expression, in which all viral transcripts accumulated in the cytoplasm. The polyclonal B-cell activator lipopolysaccharide increased the amount of viral RNA by at least twofold but did not alter the pattern of transcription. The transition from early to late expression required new protein synthesis and was blocked by the inhibitor cycloheximide. This requirement reflects the essential role of the viral Rex protein in the transition, but synthesis of cellular factors may be required as well. These results provide the first demonstration of staged viral expression in lymphocytes naturally infected by either BLV or the closely related human T-cell leukemia virus (HTLV) and validate the model of BLV and HTLV gene expression that previously was derived from transfection experiments performed mainly in nonlymphoid cells.

Animals↗
PubMed1991

Rhodococcus equi causing human pulmonary infection: review of 29 cases.

Rhodococcus equi is a gram-positive pleomorphic bacillus that has been identified as a life-threatening pulmonary pathogen in the immunocompromised host. Infection with R equi may go unrecognized by physicians unacquainted with its presentation and unaware of the organism's ability to mimic diphtheroids and to stain weakly positive with an acid-fast stain.

Actinomycetales Infections↗
PubMed1991

Episodic occurrence of antibodies against the bovine leukemia virus Rex protein during the course of infection in sheep.

Infection by bovine leukemia virus (BLV) is characterized by a long clinical latency after which some individuals develop B-cell tumors. The contributions of the viral regulatory proteins Tax and Rex during clinical latency and disease are incompletely understood. To learn about Rex expression in the host, we used a sensitive immunoprecipitation assay to detect Rex antibodies throughout the course of BLV infection in sheep. Sixty percent of the infected animals produced Rex antibodies in intermittent episodes. This pattern differed markedly from that of antibodies to virion structural proteins, which were maintained in all animals throughout infection. Only one of two animals that developed tumors had detectable Rex antibodies at the time, although the other had previously demonstrated an especially strong Rex antibody response. We examined the Rex response in the context of BLV infection by comparing it with the frequency of circulating mononuclear blood cells that could transcribe BLV RNA or produce infectious virus. Episodes of Rex antibody occurrence followed some but not all increases in the number of BLV-transcribing cells. Since the appearance of circulating antibodies requires that the intracellular Rex protein be available to serve as antigen, the episodic pattern of occurrence of Rex antibodies could result from intermittent killing by virus-specific cytotoxic cells. Fluctuations in titer that were observed during some episodes of Rex response could be due to antibody retention by antigen present in lymphoid tissue.

Animals↗
PubMed1991

Nutrition management for individuals with noninsulin-dependent diabetes mellitus in the 1990s: a review by the Diabetes Care and Education dietetic practice group.

Noninsulin-dependent diabetes mellitus (NIDDM), or Type II diabetes, is characterized by two primary defects: insulin resistance and insulin secretion. The two major goals of management of NIDDM are to achieve near normal metabolic control and to prevent/delay the microvascular and macrovascular complications of diabetes. Nutrition, exercise, and, if necessary, medication are the three primary treatment modalities used in NIDDM. Treatment regimens need to be individualized and developed with consideration for diabetes management goals and quality-of-life issues. Lean individuals with NIDDM should be encouraged to maintain their body weight and modify food composition and eating pattern to minimize glucose excursions. The primary treatment goal for an obese individual with NIDDM is weight loss. The process of teaching nutrition and meal planning involves developing a cooperative alliance, gathering information, setting realistic goals, intervention, and maintaining change. Nutrition intervention involves providing information in stages, beginning with "survival skill" information and progressing to in-depth information. The dietitian's responsibility is to promote continuity of learning by introducing new ideas and concepts and altering the learning environment. Dietitians can expand their role in the 1990s to that of a diabetes educator taking a leadership role to ensure that the individual with NIDDM receives comprehensive and individualized care.

Combined Modality Therapy↗
PubMed1990

The effect of taste on gastric and pancreatic responses in dogs.

Six mongrel dogs with gastric and esophageal fistulas (n = 4) or with gastric and pancreatic fistulas (n = 2) were studied to determine the role of taste on gastric and pancreatic secretion. Stimulation of the back of the throat with a range of tastants produced gastric acid, bicarbonate, protein, and pancreatic polypeptide levels that were statistically equivalent to those produced with stimulation of the entire tongue. This suggests that the vagus nerve is the primary mediator of the cephalic phase response to tastants. There were marked individual differences among dogs in the responses to the ten tastants that were tested. On average, monosodium glutamate and seltzer, which mongrel dogs do not normally encounter in their diets, produced lower gastric acid secretion and pancreatic polypeptide release than sweet, sour, salty, bitter, and meaty tastes. The gastric acid secreted by the dogs with esophageal fistulas in response to tastes was only one-half as large as levels previously reported for sight/smell of food and only one sixth as large as those obtained with sham feeding.

Animals↗
PubMed1989

Physiologic approaches to the control of obesity.

Morbid obesity is a major health problem in this country and throughout the world. In addition to its social stigma (in the western world), obesity exacerbates several disease states such as diabetes, hypertension, cardiac disease and restrictive lung disease. When effective medical treatment of obesity becomes available, it will depend in part upon understanding the physiologic factors that control satiety. This review summarizes the information available on brain and gut control mechanisms of satiety. Brain nuclei located in the lateral hypothalamus, ventromedial hypothalamus, and other paraventricular areas are the sites of action for potent neuropeptides, such as cholecystokinin (CCK) and neuropeptide Y, that appear to regulate feeding. Exogenous CCK has been used clinically to decrease meal size in obese patients. The sites of the satiety cascade that are most often manipulated are the gastric and intestinal phases. Physiologic gastric distension is a potent inhibitor of feeding, whereas the intermeal interval may be regulated by intestinal signals released by food in the gut. Jejunal-ileal bypass has fallen from favor and has been replaced by gastric restrictive procedures that create a small proximal gastric pouch that empties into the small bowel (gastric bypass) or the distal stomach (gastroplasty). These operations rely partially on their ability to produce gastric distension in the proximal gastric pouch at an early stage during a meal. Thus, failure results if the pouch compensates by distending or if the stoma widens with subsequent loss of slow emptying. Improved medical and surgical treatment will be designed to intervene at specific sites of the satiety cascade as knowledge of the physiologic control mechanisms of satiety increases.

Bombesin↗